Overexpression of human glutathione peroxidase protects transgenic mice against focal cerebral ischemia/reperfusion damage.
As stroke is a major cause of disability and death in the western world, there is great interest in the basic mechanisms by which ischemia/reperfusion (I/R) causes damage. To this end, extensive research has been carried out which identifies reactive oxygen species (ROS) as key participants in brain damage resultant from I/R. Brain tissue is protected from ROS damage by antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GP). Overexpression of SOD in transgenic mice has already been demonstrated to confer protection against I/R damage in murine stroke models. We are using transgenic mice overexpressing the intracellular form of glutathione peroxidase (GP1) to determine the protective capacity of overexpression of this enzyme on stroke damage. 1 h of focal cerebral ischemia followed by 24 h of reperfusion was induced using the intraliminal suture method. Volume of infarction was reduced by 48% in GP1 mice compared to nontransgenic littermates. Brain edema was reduced by 33%. Behavioral deficits agreed with histologic data. Overexpression of glutathione peroxidase confers significant protection against I/R damage in our stroke model possibly through direct scavenging of ROS or through the influencing of signalling mechanisms which lead to tissue damage.
Weisbrot-Lefkowitz
M
M
Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Reuhl
K
K
Perry
B
B
Chan
P H
PH
Inouye
M
M
Mirochnitchenko
O
O
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D005979:Glutathione Peroxidase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase